Coinfection with Different Trypanosoma cruzi Strains Interferes with the Host Immune Response to Infection

Abstract

A century after the discovery of Trypanosoma cruzi in a child living in Lassance, Minas Gerais, Brazil in 1909, many uncertainties remain with respect to factors determining the pathogenesis of Chagas disease (CD). Herein, we simultaneously investigate the contribution of both host and parasite factors during acute phase of infection in BALB/c mice infected with the JG and/or CL Brener T. cruzi strains. JG single infected mice presented reduced parasitemia and heart parasitism, no mortality, levels of pro-inflammatory mediators (TNF-α, CCL2, IL-6 and IFN-γ) similar to those found among naïve animals and no clinical manifestations of disease. On the other hand, CL Brener single infected mice presented higher parasitemia and heart parasitism, as well as an increased systemic release of pro-inflammatory mediators and higher mortality probably due to a toxic shock-like systemic inflammatory response. Interestingly, coinfection with JG and CL Brener strains resulted in intermediate parasitemia, heart parasitism and mortality. This was accompanied by an increase in the systemic release of IL-10 with a parallel increase in the number of MAC-3+ and CD4+ T spleen cells expressing IL-10. Therefore, the endogenous production of IL-10 elicited by coinfection seems to be crucial to counterregulate the potentially lethal effects triggered by systemic release of pro-inflammatory mediators induced by CL Brener single infection. In conclusion, our results suggest that the composition of the infecting parasite population plays a role in the host response to T. cruzi in determining the severity of the disease in experimentally infected BALB/c mice. The combination of JG and CL Brener was able to trigger both protective inflammatory immunity and regulatory immune mechanisms that attenuate damage caused by inflammation and disease severity in BALB/c mice.

Rhodnius prolixus Life History Outcomes Differ when Infected with Different Trypanosoma cruzi I Strains

“…90 The length of acute parasitemia is highly variable among T. cruzi-infected vertebrate hosts, with some hosts exhibiting long-lasting high parasitemias and others moving from an acute stage to a chronic stage with low parasitemia in a matter of weeks. 1,88,89 In spite of all of this attention to the varied effects of T. cruzi on vertebrate hosts, until now, there has been relatively little attention to variation in its effect on its invertebrate hosts.…”

The Use of a Heterogeneously Controlled Mouse Population Reveals a Significant Correlation of Acute Phase Parasitemia with Mortality in Chagas Disease

“…This specific F2 population was generated by intercrossing littermates derived from the breeding of the highly susceptible A/J with the highly resistant C57BL/6 mouse strains. Divergence in susceptibility to T. cruzi infection has been previously reported for different inbred mouse strains [19], [23], [30]–[33]. In studies specifically addressing the susceptibility to the Y strain of T. cruzi , it has been shown that mice from the A/J inbred strain succumb to infection, whereas C57BL/6 mice survive to the acute phase when infected with low inoculum (∼1000 forms) [22], [23].…”

Experimental Chagas disease in Balb/c mice previously vaccinated with T. rangeli. II. The innate immune response shows immunological memory: Reality or fiction?

“…In the infection by T. cruzi, both early interaction between the host cell and the parasite and the development of a suitable microenvironment of cytokines are critical aspects in controlling parasitemia (Rodrígues et al, 2010). In this sense, the efficiency of the microbicidal function depends on the participation of proinflammatory cytokines produced by NK, Th1 cells and macrophages, among others.…”

“…In this sense, lower synthesis of this cytokine was observed in V-I animals in relation to I animals. It is known that IL-10 neutralizes the function of TNF ␣ and regulates the synthesis of metalloproteases, IFN␥, IL-6, and NO (Rodrígues et al, 2010;Hovsepian et al, 2013). However, it is postulated that an excessive production of IL-10, particularly in early stages, might be, among other factors, responsible for the susceptibility to infection by T. cruzi (Basso et al, 2004).…”